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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

WNK4 Gene

protein-coding GIFtS: 59
GCID: GC17P040932

WNK lysine deficient protein kinase 4

(Previous names: protein kinase, lysine deficient 4 )
(Previous symbol: PRKWNK4)

Explore 16 diseases affiliated with
WNK4 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
WNK Lysine Deficient Protein Kinase 4¹ ²		PHA2B² ⁵
PRKWNK4¹ ² ³ ⁵		Protein Kinase, Lysine Deficient 4¹
Protein Kinase Lysine-Deficient 4² ³		Serine/Threonine-Protein Kinase WNK4²
Protein Kinase With No Lysine 4² ³		EC 2.7.11⁸
EC 2.7.11.1³ ⁸

External Ids:	HGNC: 14544¹	Entrez Gene: 65266²	Ensembl: ENSG00000126562⁷	OMIM: 601844⁵	UniProtKB: Q96J92³

Export aliases for WNK4 gene to outside databases

Previous GC identifers: GC17P038188 GC17P036697

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for WNK4:

This gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight

junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The kinase

regulates the activities of several types of ion channels, cotransporters, and exchangers involved in electrolyte flux

in epithelial cells. Mutations in this gene result in pseudohypoaldosteronism type IIB.(provided by RefSeq, Sep 2009)

UniProtKB/Swiss-Prot: WNK4_HUMAN, Q96J92

Function: Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell

signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters

and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6.

Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to

prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent

mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4

appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to

maintain integrated homeostasis. Phosphorylates NEDD4L

Gene Wiki entry for WNK4

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000017.10 NC_018928.1 NT_010783.15

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the WNK4 gene promoter:
STAT1 Pax-5 SREBP-1c STAT1beta CUTL1 STAT1alpha SREBP-1b Roaz SREBP-1a RSRFC4
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: WNK4 promoter sequence

Search SABiosciences Chromatin IP Primers for WNK4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat WNK4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q21-q22 Ensembl cytogenetic band: 17q21.31 HGNC cytogenetic band: 17q21-q22

WNK4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
WNK4 gene location

GeneLoc information about chromosome 17 GeneLoc Exon Structure

GeneLoc location for GC17P040932: view genomic region (about GC identifiers)

Start:	40,932,649 bp from pter	End:	40,949,084 bp from pter
Size:	16,436 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: WNK4_HUMAN, Q96J92 (See protein sequence)

Recommended Name: Serine/threonine-protein kinase WNK4

Size: 1243 amino acids; 134739 Da

Cofactor: Magnesium (By similarity)

Subunit: Interacts with the C-terminal region of KCNJ1 (By similarity). Interacts with WNK1 and WNK3 (By similarity)

Subcellular location: Cell junction, tight junction (By similarity). Note=Present exclusively in intercellular

junctions in the distal convoluted tubule and in both the cytoplasm and intercellular junctions in the cortical

collecting duct. WNK4 is part of the tight junction complex (By similarity)

Caution: Cys-203 is present instead of the conserved Lys which is expected to be an active site residue. Lys-186

appears to fulfill the required catalytic function

Sequence caution: Sequence=BAC04669.1; Type=Erroneous initiation; Note=Translation N-terminally extended;

Sequence=CAC48387.1; Type=Frameshift; Positions=4;

1 PDB 3D structure from and Proteopedia for WNK4:

2V3S (3D)

Secondary accessions: Q8N8X3 Q8N8Z2 Q96DT8 Q9BYS5

Alternative splicing: 3 isoforms: Q96J92-1 Q96J92-2 Q96J92-3 (No experimental confirmation available. Incomplete sequence)

Explore the universe of human proteins at neXtProt for WNK4: NX_Q96J92

Post-translational modifications:

Phosphorylated by WNK1 and WNK3 (By similarity)¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q96J92

4/10 DME Specific Peptides for WNK4 (Q96J92) (see all 10)

EYPYSEC

ILHRDLK

EIGRGSF

FGMCMLEM

WNK4 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_115763.2

ENSEMBL proteins:

ENSP00000246914 ENSP00000467088 ENSP00000467312

Human Recombinant Protein Products for WNK4:

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	Novus Biologicals WNK4 Proteins Novus Biologicals WNK4 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for WNK4

Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	IEA	--
GO:0005923	tight junction	ISS	--

WNK4 for ontologies About GeneDecksing

WNK4 Antibody Products:

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	ThermoFisher Antibodies for WNK4

Assay Products for WNK4:

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	GenScript Custom Assay Services for WNK4
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for WNK4

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

WNK4 for domains About GeneDecksing

4 InterPro domains/families:

IPR011009 Kinase-like_dom

IPR024678 Kinase_OSR1/WNK_CCT

IPR008271 Ser/Thr_kinase_AS

IPR000719 Prot_kinase_cat_dom

Graphical View of Domain Structure for InterPro Entry Q96J92

ProtoNet protein and cluster: Q96J92

UniProtKB/Swiss-Prot: WNK4_HUMAN, Q96J92

Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WNK subfamily

Similarity: Contains 1 protein kinase domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: WNK4_HUMAN, Q96J92

Function: Serine/threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell

signaling, survival and proliferation. Acts as an activator and inhibitor of sodium-coupled chloride cotransporters

and potassium-coupled chloride cotransporters respectively. Activates SCNN1A, SCNN1B, SCNN1D, SGK1, TRPV5 and TRPV6.

Regulates the activity of the thiazide-sensitive Na-Cl cotransporter, SLC12A3, by phosphorylation which appears to

prevent membrane trafficking of SLC12A3. Also inhibits the renal K(+) channel, KCNJ1, via a kinase-independent

mechanism by which it induces clearance of the protein from the cell surface by clathrin-dependent endocytosis. WNK4

appears to act as a molecular switch that can vary the balance between NaCl reabsorption and K(+) secretion to

maintain integrated homeostasis. Phosphorylates NEDD4L

Catalytic activity: ATP + a protein = ADP + a phosphoprotein

Enzyme regulation: Activation requires autophosphorylation of Ser-335. Phosphorylation of Ser-331 also promotes

increased activity (By similarity)

Enzyme Numbers (IUBMB): EC 2.7.11.1¹ ² EC 2.7.11²

Gene Ontology (GO): 3 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004674	protein serine/threonine kinase activity	ISS	--
GO:0005515	protein binding	--	--
GO:0005524	ATP binding	ISS	--

WNK4 for ontologies About GeneDecksing

Phenotypes:
4 GenomeRNAi human phenotypes for WNK4:

Increased cell death HMECs cel

Increased cell spreading

Increased colony dispersion (i

Upregulation of Wnt/beta-caten

4 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Wnk4):

cardiovascular system

homeostasis/metabolism

no phenotypic analysis

renal/urinary system

WNK4 for phenotypes About GeneDecksing

Animal Models:
Mouse knock-outs for WNK4: Wnk4^tm2.1Suc Wnk4^tm1Pfi

inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for WNK4

miRNA Products:		miRTarBase miRNAs that target WNK4: hsa-mir-296-5p (MIRT004559)

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		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat WNK4
		8/11 QIAGEN miScript miRNA Assays for microRNAs that regulate WNK4 (see all 11):
		hsa-miR-140-5p hsa-miR-502-5p hsa-miR-563 hsa-miR-26b* hsa-miR-1291 hsa-miR-380* hsa-miR-654-5p hsa-miR-1207-3p

		SwitchGear 3'UTR luciferase reporter plasmid: WNK4 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for WNK4 (see all 7) OriGene shRNA RFP: WNK4 OriGene siRNA: WNK4
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Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for WNK4 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for WNK4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for WNK4

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Cell adhesion Tight junctions

Cell adhesion Tight junctions

1.00

Cell adhesion_Tight junctions

0.99

Diuretics Pathway, Pharmacodynamics

Diuretics Pathway, Pharmacodynamics

1.00

PI3K / Akt Signaling

PI3K / Akt Signaling

1.00

Pathway sources
See GeneCards unified pathways
Show all pathways

1 EMD Millipore Pathway for WNK4

Cell adhesion Tight junctions

1 Cell Signaling Technology (CST) Pathway for WNK4

PI3K / Akt Signaling

1 GeneGo (Thomson Reuters) Pathway for WNK4

Cell adhesion Tight junctions

1 PharmGKB Pathway for WNK4

Diuretics Pathway, Pharmacodynamics

WNK4 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for WNK4

STRING Interaction Network Preview (showing 5 interactants - click image to see 15)

5/55 Interacting proteins for WNK4 (Q96J92^{2, 3} ENSP00000246914⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 55)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
OXSR1	O95747²^,³, ENSP00000311713⁴	MINT-5207699 MINT-5207631 MINT-5207540 MINT-5207597 MINT-5207682 MINT-5207580 MINT-5207648 MINT-5207716 MINT-5207665 MINT-5207614 MINT-5207558 I2D: score=1 STRING: ENSP00000311713
YWHAQ	P27348²^,³, ENSP00000238081⁴	MINT-7900157 I2D: score=1 STRING: ENSP00000238081
ESR2	Q92731³, ENSP00000343925⁴	I2D: score=1 STRING: ENSP00000343925
STK39	Q9UEW8³, ENSP00000348278⁴	I2D: score=3 STRING: ENSP00000348278
SLC12A3	P55017³, ENSP00000262502⁴	I2D: score=1 STRING: ENSP00000262502

About this table

Gene Ontology (GO): 5/7 biological process terms (GO ID links to tree view) (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006468	protein phosphorylation	ISS	--
GO:0006811	ion transport	ISS	--
GO:0006821	chloride transport	IEA	--
GO:0007243	intracellular protein kinase cascade	ISS	--
GO:0008104	protein localization	IEA	--

WNK4 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

WNK4 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for WNK4

4 HMDB Compounds for WNK4 About this table

Compound	Synonyms	CAS #	PubMed Ids
ADP	adenosindiphosphorsaeure (see all 8)	58-64-0	--
Adenosine triphosphate	5'-(tetrahydrogen triphosphate) Adenosine (see all 24)	56-65-5	--
Chlorine	Cl2 (see all 13)	16887-00-6	--
Magnesium	Magnesium (see all 2)	7439-95-4	--

9 Novoseek chemical compound relationships for WNK4 gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
thiazide	71	2	15639021 (1), 17975670 (1)
lysine	68.9	19	15639021 (2), 14769928 (2), 14616768 (1), 19706464 (1) (see all 11)
nacl	59.7	18	15841204 (2), 19401467 (2), 15796898 (2), 16820787 (1) (see all 13)
threonine	58	3	19690383 (1), 18547946 (1), 17647025 (1)
potassium	55.8	14	15300163 (3), 15639021 (1), 18695394 (1), 15081430 (1) (see all 10)
chloride	48.9	6	15300163 (3), 15639021 (1), 15637347 (1), 17194447 (1)
serine	45.8	3	19690383 (1), 19706464 (1), 18547946 (1)
sodium	42.1	5	18277144 (2), 15639021 (1), 18695394 (1), 19690383 (1)
proline	39.9	2	16173916 (1), 19587141 (1)

Search CenterWatch for drugs/clinical trials and news about WNK4

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, Sirion Biotech, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for WNK4 gene:

NM_032387.4

Unigene Cluster for WNK4:

WNK lysine deficient protein kinase 4

Hs.105448 [show with all ESTs]

Unigene Representative Sequence: NM_032387

6 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000246914(uc002ibj.3 uc010wgx.2 uc002ibk.1 uc010wgy.1)

ENST00000591448 ENST00000592669 ENST00000587705 ENST00000592072 ENST00000587745

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		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat WNK4
		8/11 QIAGEN miScript miRNA Assays for microRNAs that regulate WNK4 (see all 11):
		hsa-miR-140-5p hsa-miR-502-5p hsa-miR-563 hsa-miR-26b* hsa-miR-1291 hsa-miR-380* hsa-miR-654-5p hsa-miR-1207-3p

		SwitchGear 3'UTR luciferase reporter plasmid: WNK4 3' UTR sequence

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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat WNK4

Additional cDNA sequence:

AF390018.1 AJ309861.1 AJ316534.1 AK096003.1 AK096052.1 AK301963.1 BC136664.1 BC144356.1

6 DOTS entries:

DT.91746101 DT.100022245 DT.95224531 DT.100789457 DT.92025546 DT.92052927

24/66 AceView cDNA sequences (see all 66):

BM683764 AA687630 NM_032387 AJ316534 AK096003 AW135316 AI244885 AA877924

CA388931 CA388932 AJ309861 AF390018 BX118400 AA513292 AI650786 AL041763

CD633911 BG824713 CD633905 CD633909 AA700228 AW275318 BQ446383 CD633901

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

WNK4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: --

About this image

WNK4 expression in embryonic tissues and stem cells
Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Kidney

Distal Tubule

Distal Tubule Cells

Kidney

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See WNK4 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for WNK4

SOURCE GeneReport for Unigene cluster: Hs.105448

UniProtKB/Swiss-Prot: WNK4_HUMAN, Q96J92

Tissue specificity: Expressed in kidney, colon and skin

SABiosciences Custom PCR Arrays for WNK4

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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat WNK4

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for WNK4

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of eukaryotes.

Orthologs for WNK4 gene from 7/22 species (see all 22) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	LOC777580¹	serine/threonine-protein kinase WNK4-like	64.06(n) 62.8(a)		777580 XM_003642827.1 XP_003642875.1
lizard (Anolis carolinensis)	Reptilia	-- WNK4⁶	--	9(a) 34(a)	possible ortholog 1 ↔ 1	1(205439218-205490633) 6(62130032-62275525)
zebrafish (Danio rerio)	Actinopterygii	LOC100330953¹	serine/threonine-protein kinase WNK4-like	62.63(n) 60.61(a)		100330953 XM_002663887.2 XP_002663933.2
fruit fly (Drosophila melanogaster)	Insecta	Wnk⁶	--	11(a)	1 → many	3L(21536950-21548028)
worm (Caenorhabditis elegans)	Secernentea	wnk-1⁶	mammalian WNK-type protein kinase homolog family m...	17(a)	1 → many	IV(9200100-9212216)
thale cress (Arabidopsis thaliana)	eudicotyledons	AT5G55560⁶ WNK3⁶ (see all 11)	putative serine/threonine-protein kinase WNK3 (see all 11)	40(a) 33(a) (see all 11)	many ↔ many many ↔ many (see all 11)	5(22506302-22507879) 3(17873012-17875220)
rice (Oryza sativa)	Liliopsida	AK100930.1²	--	73.32(n)		AK100930.1

ENSEMBL Gene Tree for WNK4 (if available)
TreeFam Gene Tree for WNK4 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for WNK4 gene

WNK1² NRBP1² WNK2² NRBP2² WNK3²

18/26 SIMAP similar genes for WNK4 using alignment to 4 protein entries: WNK4_HUMAN (see all proteins) (see all similar genes):

CAMK2A PKN2 BRAF STK11 NEK6 NEK9

ULK1 STK25 WNK2 BRSK2 MAPK3 NRBP2

CDK3 CDK4 MARK4 STK17A DAPK1 NEK7

WNK4 for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 17 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs137853093^1,2	C	pathogenic	40939503(+)	`AGCCAA/GAGGCA`	2	K E	mis¹		0	--	--	--	--
rs137853094^1,2	C	pathogenic	40939510(+)	`GGCAGA/CCCAGC`	2	D A	mis¹		0	--	--	--	--
rs137853092^1,2	C	pathogenic	40939512(+)	`CAGACC/GAGCAC`	2	Q E	mis¹		0	--	--	--	--
rs137853095^1,2	C	pathogenic	40948262(+)	`CCAGCC/TGCCAG`	2	R C	mis¹		0	--	--	--	--
rs113406387^1,2	C	--	40930659(+)	`ATTTTC/TACGGC`	2	--	int¹ us2k¹		2		CSA WA	120
rs61754283^1,2	F	--	40930827(+)	`GGAGTG/ACCTGG`	2	--	int¹ us2k¹		3		NS	2236
rs61754284^1,2	F	--	40930851(+)	`CAGCTG/CTAGCA`	2	--	us2k¹ int¹		3		NS	2236
rs61754306^1,2	C,F	--	40930888(+)	`CTCTGG/AGAGGT`	2	--	int¹ us2k¹		3		NS	2236
rs201145202^1,2		--	40930961(+)	`CCTATC/TTCTCC`	2	--	int¹ us2k¹		0	--	--	--	--
rs139710182^1,2	C	--	40931092(+)	`GCAGGA/GACCTG`	2	--	ut3¹ us2k¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for WNK4 (40932649 - 40949084 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV) variations for WNK4: --
Human Gene Mutation Database (HGMD): WNK4

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

WNK4 for disorders           About GeneDecksing

OMIM gene information: 601844
OMIM disorders: 145260
UniProtKB/Swiss-Prot: WNK4_HUMAN, Q96J92

Defects in WNK4 are a cause of pseudohypoaldosteronism type 2B (PHA2B) [MIM:614491]. PHAII is an autosomal

dominant disease characterized by severe hypertension, hyperkalemia, and sensitivity to thiazide diuretics which may

result from a chloride shunt in the renal distal nephron

16 diseases for WNK4: About MalaCards

pseudohypoaldosteronism glucocorticoid-remediable aldosteronism pseudohypoaldosteronism type iib pseudohypoaldosteronism type ii

autosomal dominant disease essential hypertension liddle syndrome hypercalciuria

hypertension aldosteronism cystic fibrosis osteoporosis

fibrosis choroiditis pancreatitis loeys-dietz syndrome

4 diseases from the University of Copenhagen DISEASES database for WNK4:

Pseudohypoaldosteronism Hypertension Liddle syndrome Metabolic acidosis

9 Novoseek disease relationships for WNK4 gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
pseudohypoaldosteronism	96.5	23	15300163 (2), 16173916 (1), 15796898 (1), 19016006 (1) (see all 21)
gordon syndrome	95	6	19470686 (1), 18277144 (1), 16683163 (1), 15866321 (1) (see all 6)
hyperkalemia	87.2	21	15696009 (2), 12515852 (2), 17360471 (2), 18695394 (1) (see all 15)
hyperchloremia	77.6	1	12515852 (1)
genetic hypertension	68.3	3	15309683 (1), 16501604 (1)
essential hypertension	60.4	10	19340547 (4), 14967840 (2), 12719438 (1), 15866321 (1) (see all 6)
metabolic acidosis	56	1	12515852 (1)
hypertension arterial	31.7	2	16173916 (1), 18701621 (1)
hypotension	1.69	2	15309683 (1)

Genetic Association Database (GAD): WNK4
Human Genome Epidemiology (HuGE) Navigator: WNK4 (12 documents)

Export disorders for WNK4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for WNK4 gene, integrated from 9 sources (see all 97):
(articles sorted by number of sources associating them with WNK4)

Utopia: connect your pdf to the dynamic
world of online information

Identification of 108 SNPs in TSC, WNK1, and WNK4 and their association with hypertension in a Japanese general population. (PubMed id 15309683)^{1, 4, 9} Kokubo Y....Miyata T. (2004)
Genetic variants of WNK4 in whites and African Americans with hypertension. (PubMed id 12719438)^{1, 4, 9} Erlich P.M....DeStefano A.L. (2003)
WNK4 intron 10 polymorphism is not associated with hypertension. (PubMed id 14967840)^{1, 4, 9} Speirs H.J. and Morris B.J. (2004)
The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics. (PubMed id 15824464)^{1, 4, 9} Matayoshi T....Kawano Y. (2004)
Association of EDNRA, but not WNK4 or FKBP1B, polymorphisms with essential hypertension. (PubMed id 14616768)^{1, 4, 9} Benjafield A.V....Morris B.J. (2003)
Serum and glucocorticoid-induced kinase (SGK) 1 and t he epithelial sodium channel are regulated by multiple with no lysine (WNK) fam ily members. (PubMed id 20525693)^{1, 2} Heise C.J....Cobb M.H. (2010)
Complete sequencing and characterization of 21,243 full-length human cDNAs. (PubMed id 14702039)^{1, 2} Ota T.... Sugano S. (2004)
[Correlation analysis between WNK4 gene and essential hypertension] (PubMed id 12905707)^{1, 4} Sun Z.J....Zhao Y.Y. (2003)
WNK kinases, a novel protein kinase subfamily in multi-cellular organisms. (PubMed id 11571656)^{1, 2} Verissimo F. and Jordan P. (2001)
Human hypertension caused by mutations in WNK kinases. (PubMed id 11498583)^{1, 2} Wilson F.H.... Lifton R.P. (2001)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 65266	HGNC: 14544	AceView: PRKWNK4	Ensembl:ENSG00000126562	euGenes: HUgn65266
ECgene: WNK4	H-InvDB: WNK4

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for WNK4	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/WNK4

Intellectual Property for WNK4 gene
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Patent Information for WNK4 gene:
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GeneCards and IP:
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WNK4 Gene

WNK lysine deficient protein kinase 4

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WNK4 Gene

WNK lysine deficient protein kinase 4

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